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A series of 2-aryl-5-[4-(1H-pyrrol-1-yl)phenyl]-1,3,4-oxadiazole derivatives (VIa-g) have been synthesized in good yields. These compounds were synthesized with an approach to reduce the growing anti-tubercular resistance and to develop more potent and less side effects having antitubercular activity. The reaction of 2,5-dimethoxytetrahydro furan with 4-aminobenzoate (II) in presence of ethanol, which yields ethyl 4-pyrrol-1-yl benzoate (III). This ethyl-4-pyrrol-1-yl benzoate (III) on reaction with hydrazine hydrate produced 4-pyrrol-1-yl benzoic acid hydrazide (IV). This carbohydrazide on treatment with different substituted benzoyl chlorides gave intermediates (Va-g), which on cyclisation with P2O5 in the presence of DMF yielded of 2-aryl-5-[4-(1Hpyrrol-1-yl)phenyl]-1,3,4-oxadiazoles VI(a-g). Structure of newly synthesized pyrrole derivatives were confirmed on the basis of physicochemical and spectral data (IR, 1H-NMR, 13C-NMR and Mass spectra). All the synthesized compounds were screened for their antitubercular activity using Microplate Alamar Blue Assay (MABA) method. Compounds showed anti-tubercular activity at MIC values between 1.6 to 12.5 µg/ml, compounds VIb,VIc and VId showed highest activity of 1.6 µg/ml. Selected compounds were evaluated for anti-bacterial activity against gram positive (S. aureus) and gram negative (E. coli). Compounds showed moderate activity. Physicochemical properties of the selected compounds satisfieds with the Lipinski’s rule of 5.

New series of pyrrolylpyranopyrazole were synthesized by reacting with (one pot synthesis) ethyl acetoacetate in aqueous ethanol (1), hydrazine hydrate (2), substituted aldehydes (3a-g), malononitrile (4) and triethylamine’s base stirring for 5hr the solid precipitate was obtained, it has been filtered and washed with cold water to give 6-amino-3-methyl-4-substituted phenyl-1,3a,4,7a-tetrahydropyrano [2,3-c] pyrazole-5-carbonitrile (5a-g). Further it is reacted with 4- pyrrol-1-yl benzoic acid (6) with substituted pyranopyrazoline presence of HBTU and DIEA which resulting in formation of substituted N-5-cyano-3-methyl-4-substituted phenyl 1,3a,47a-tetrahydropyrano [2,3-c] pyrazol-6-yl)-4-(1H-pyrrol-1-yl) benzamides (7a-g) was obtained. All newly synthesized compounds were confirmed by TLC and melting point. The structure of the all newly synthesized compounds were confirmed by spectral study such as IR, 1H NMR, 13C NMR and Mass spectroscopy. The newly synthesized compounds were screened for their antibacterial and antitubercular activities. Compounds exhibited antitubercular activity in the range of 1.6 to 25 µg/ml (MIC). Compounds showed antibacterial activity in the range of 0.8 to 100 µg/ml (MIC). It was indeed very much encouraging to note that most of the compounds have shown better and significant antibacterial and antitubercular activities.

The various novel nitrogen containing heterocyclic compounds were synthesized and are screened for antibacterial and antitubercular activities, purity of newly synthesized compounds confirmed by using TLC and structures for the same compounds were confirmed by using IR, NMR, 13C and Mass spectrum. Pyrrole ring was constructed by reacting benzocaine with 2, 5-dimethoxytetrahydrofuran in presence of glacial acetic acid to obtain ethyl 4-pyrrol-1-ylbenzoate (2) in good yield. Conversion of ethyl 4-pyrrol-1-ylbenzoate (2) into 4-pyrrol-1-yl-benzoic acid hydrazide (3), which was achieved by refluxing ethyl 4-pyrrol-1-ylbenzoate (2) with hydrazine hydrate in ethanol. Then this 4-pyrrol-1-yl-benzoic acid hydrazide (3) treated with appropriate benzaldehyde in presence of TCCA and ethanol to yield compound substituted 2-(4-(1H-pyrrol-1-yl)phenyl)-5-phenyl-1,3,4-oxadiazole 04(a-f).Structures of newly synthesized compounds were confirmed on the basis of physico-chemical and spectral data (IR, 1H &13C-NMR, Mass spectra). All the synthesized compounds were screened for anti-tubercular activity using Microplate Almar Blue Assay (MABA) method. Compounds showed anti-tubercular activity at MIC values between 50 to 3.12 µg/ml when compared with standard drugs Pyrazinamide (3.125 µg/ml) and Streptomycin (6.25 µg/ml).Newly synthesised compounds were also screened for antibacterial activity using broth micro dilution assay method. Compounds showed antibacterial activity at MIC values between 25 to 0.8 µg/ml when compared with standard drugs Ciprofloxacin and Norfloxacin.

Thiazolidinedione (TZD) based medications have demonstrated to enhance the insulin sensitivity control, hyperglycemia, and lipid metabolism in patients with type 2 diabetes. Hence, in this study, a new series of novel coumarin-4-yl-1,2,3-triazol-4-yl-methyl-thiazolidine-2,4-diones (TZD1-TZD18) were synthesized via copper (I)-catalyzed azide-alkyne cycloaddition "Click Chemistry". The synthesized compounds were evaluated for their glucose uptake assay and in vitro cytotoxicity against HEK-293 (human embryonic kidney) cells which were compared with the standard drug Pioglitazone. Further, molecular docking analysis of these compounds was carried out to explain the in vitro results with PPARγ (PDB ID: 3CS8) and to better understand the bonding interactions with the target protein. The outcomes of in vitro assessment, molecular docking, and pharmacokinetics of the title compounds were revealed to be highly correlated. Interestingly, the compounds TZD4, TZD10, TZD14 and TZD16 were most efficient in lowering the blood glucose level compared with standard drug.

Enoyl Acyl Carrier Protein (ACP) Reductase, a key enzyme, which catalyzes the last reductive step of fatty acid biosynthesis and it, is one of the key enzymes for the development of antitubercular agents. In this pursuit, molecular docking and 3D-QSAR studies (CoMFA and CoMSIA) have been performed on a series of pyrimidine derivatives (29 compounds) to understand the binding sites, interactions to improve over the existing leads in terms of improved biological and physico-chemical properties. Molecular docking was performed on a protein InhA (T2A mutant) (PDB ID: 5OIR) using the Surflex-Dock suite available in SYBYL-X 2.1.1 (Tripose Inc., USA). In addition, 3D-QSAR studies have been performed to validate the models using the data set, which was segregated into training and test set by using the Diversity and Dissimilarity method. Structural features required for the prediction of better inhibitory potency was generated in the form of contour maps from the CoMFA and CoMSIA models (Steric, Electrostatic, Hydrophobicity, H-bond donor and acceptor maps) and predicted values for r2 = 0.966, q2 = 0.22 for the CoMFA model and r2 = 0.925, q2 = 0.576 for the CoMSIA model. From this study, it is observed that interaction with amino acid residues TYR158, MET199, MET161, GLY96, and PHE97 are important for the activity that helped to predict SARs by providing important structural features. Both the models were good in understanding the specific activity of some of the compounds that will facilitate to develop new types of Enoyl ACP reductase inhibitors.

Objective In the present study a series of eleven bis-heterocyclic compounds with indole derivative carrying 1,2,4-triazole moiety were synthesized and assessed for their in vitro α-amylase and α-glucosidase inhibition activity. Method The synthesized compounds were characterized by using various spectroscopic techniques such as 1H NMR, IR and EI-MS. Initial in silico screening process was used to find potential ligands that were later evaluated for α-amylase and α-glucosidase inhibitory potential. Results The docking results revealed that the synthesized compounds were well accommodated in the binding pockets of α-glucosidase. Especially, 5e and 5j showed similar interaction pattern, as previously reported Casuarine-enzyme complex. In vitro analysis suggests that compounds 5a-5k showed varying degrees of α-amylase and α-glucosidase inhibitory activity. Amongst them, 5e and 5j demonstrated good enzyme inhibition while remaining compounds showed low to moderate inhibitory potential. Conclusions Addition of 2,5 dimethoxy substituent (2,5-dimethoxybenzaldehyde) (5e) or hydroxy, methoxy substituents (6-methoxy-2-naphthol aldehyde) (5j) at ortho and meta position exhibited good α-amylase and α-glucosidase inhibition. Hence this study provides several insights on improving the pharmacological profile of triazole containing compounds that can be adopted to design and develop novel glucosidase inhibitors.

The antibacterial target, enoyl-acyl carrier protein (ACP) reductase, is a homotetrameric enzyme that catalyzes the last reductive step of fatty acid biosynthesis. In the present paper, Surflex docking has been carried out on a series (10 compounds) of enoyl ACP reductase inhibitors, using the SYBYL-X 2.0 package (Tripos Inc., St. Louis, USA). Surflex-docking studies revealed that the carbonyl group and pyrazole ring were significant for binding to the receptor, and it is also found that the pattern of binding of tested compounds is same as that of the 4TZK ligand, this in turn helped in understanding of specific activity of compounds.

Since 2019, the infection of SARS‐CoV‐2 has been spreading worldwide and caused potentially lethal health problems. In view of this, the present study explores the most commodious and environmentally benign synthetic protocol for the synthesis of tetrahydrobenzo[b]pyran and pyrano[2,3‐d]pyrimidinones as SARS‐CoV‐2 inhibitors via three‐component cycloaddition of aromatic aldehyde, malononitrile, and dimedone/barbituric acid in water. Lemon peel from juice factory waste, namely, lemon ( Citrus limon ), sweet lemon ( C. limetta ), and Kaffir lime or Citron ( C. hystrix ), effectually utilized to obtain WELPSA, WESLPSA, and WEKLPSA, respectively, for the synthesis of title compounds. The catalyst was characterized by scanning electron microscope (SEM) and energy‐dispersive x‐ray spectroscopy (EDX). The concentration of sodium, potassium, calcium, and magnesium in the catalyst (WELPSA) was determined using atomic absorption spectrometry (AAS). The current approach manifests numerous notable advantages that include ease of preparation, handling and benignity of the catalyst, low cost, green reaction conditions, facile workup, excellent yields (93%–97%) with extreme purity, and recyclability of the catalyst. Compounds were docked on the crystal structure of SARS‐CoV‐2 (PDB: 6M3M). The consensus score obtained in the range 2.47–4.63 suggests that docking study was optimistic indicating the summary of all forces of interaction between ligands and the protein., Since 2019, the infection of SARS‐CoV‐2 has been spreading worldwide and caused potentially lethal health problems. In view of this, the present study explores the most commodious and environmentally benign synthetic protocol for the synthesis of tetrahydrobenzo[b]pyran and pyrano[2,3‐d]pyrimidinones as SARS‐CoV‐2 inhibitors via three‐component cycloaddition of aromatic aldehyde, malononitrile, and dimedone/barbituric acid in water. The use of green catalyst WELPSA obtained from the agricultural wastes is the major addition to this protocol.

β-Secretase (BACE1) has been broadly documented as one of the possible therapeutic targets for the treatment of Alzheimer's disease. In this paper, we report the synthesis and the for β-secretase (BACE-1) inhibitory activity of new series of tetrahydrobenzo [b] pyran derivatives. One-pot synthesis of tetrahydrobenzo [b] pyrans was carried out by condensing aromatic aldehyde, malononitrile and 1,3-cyclohexanedione using ionic liquid 1-butyl-3-methyl imidazolium chloride ([bmIm]Cl-) in aqueous alcohol media. The addition of alcohol and water in the ratio of 1:2 keeps all the reactants in solution which facilitates the reaction and makes the product formation very easy. The synthesized compounds were subjected to BACE1 inhibition assay and six compounds, 4d, 4e, 4f, 4h, 4i, and 4p have shown significant IC50 values at micromolar level. Among these six active compounds, 4e was a potential inhibitor with its IC50 value in nanomolar range. All the synthesized compounds were docked onto the active site of β-Secretase enzyme.

In an effort to produce new lead antimycobacterial compounds, herein we have reported the synthesis of a sequence of new pyrrolyl benzamide derivatives. The new chemical entities were screened to target enoyl-ACP reductase enzyme, which is one of the key enzymes of M. tuberculosis that are involved in type II fatty acid biosynthetic pathway. Compound 3q exhibited H-bonding interactions with Tyr158, Thr196 and co-factor NAD+ that binds the active site of InhA. All the pyrrolyl benzamide compounds were evaluated as inhibitors of M. tuberculosis H37Rv as well as inhibitors of InhA. Among them, few representative compounds were tested for mammalian cell toxicity on the human lung cancer cell-line (A549) and MV cell line that presented no cytotoxicity. Five of these compounds exhibited a good activity against InhA.

Background A hybrid molecule of different biologically active substances can improve affinity and efficiency compared to a standard drug. Hence based on this fact, we predict that a combination of fluorine, oxadiazole, sulfur, etc., may enhance α-glucosidase inhibition activity compared to a standard drug. Methods A series of novel 5-(2,5-bis(2,2,2-trifluoroethoxy)phenyl)-1,3,4-oxadiazole-2-thiol derivatives (2a-2i) were synthesized and characterized using spectroscopic techniques such as 1HNMR and LC-MS. In order to evaluate its bioactivity, in vitro α-amylase and α-glycosidase inhibitory activity were performed. In vivo study was carried using a genetic model, Drosophila melanogaster, for assessing the antihyperglycemic effects. Results The compounds 2a-2i demonstrated α-amylase inhibitory activity in the range of IC50 = 40.00–80.00 μg/ml as compare to standard acarbose (IC50 = 34.71 μg/ml). Compounds 2a-2i demonstrated α-glucosidase inhibitory activity in the range of IC50 = 46.01–81.65 μg/ml as compared to standard acarbose (IC50 = 34.72 μg/ml). Docking studies on a target protein, N-terminal subunit of human Maltase-glucoamylase (PDB:2QMJ) was carried and the compounds were found to dock into the active site of the enzyme (Fig. 1). The predicted binding energies of the compounds were calculated. The in vitro studies indicate that compounds 2b and 2g had better activity among the synthesized compounds. Whereas in vivo study indicates that 2b, 2g, and 2i could lower glucose levels in the Drosophila, but then 17–30% reduced capacity than acarbose and may be overcome by adjusting their dosage. Conclusions The in vitro and in vivo studies indicate that compounds 2b and 2g had better activity among the synthesized compounds. This study has recognized that compounds like 2b, 2g, and 2i may be considered potential candidates for further developing a novel class of antidiabetic agents.

An efficient, high yields and rapid synthesis of N-tert-butyl-4-(4-substituted phenyl)-2-((substituted-2-oxo-2H-chromen-4-yl)methylthio)-6-oxo-1,6-dihydropyrimidine-5-carboxamide derivatives (4a–4j) under microwave-irradiation has been described. All the newly synthesized compounds (4a–4j) were characterized by elemental analysis and spectroscopic studies. The synthesised compounds (4a–4j) were evaluated for their antibacterial activity by agar-well diffusion method and anti-inflammatory activity by egg albumin denaturation method. The compound (4f) exhibits antibacterial effect with MIC–2.5 μg/mL against gram positive S. aureus bacterial strain compared to standard ciprofloxacin drug (MIC–10 μg/mL). The compound (4c) shows an inhibition of heat induced protein denaturation 75.42% at a concentration of 31.25 μg/ml and is almost ten times more active than compared to standard aceclofenac drug (5.50%). Molecular docking study has been performed for all the synthesized compounds with S. aureus dihydropteroate synthetase (DHPS) and results obtained are quite promising.

P70-S6K1 & PI3K-δ kinases are identified to be involved in many physiological processes associated with cancer, therefore many of the inhibitors being designed to target these kinases are in clinical trials. In the current study we have exploited the N-9 substituted 6-(4-(4-propoxyphenyl) piperazin-1-yl)-9H-purine derivatives for their inhibitory properties with the above kinases. We have used an in silico docking study with seventeen purine derivatives for their binding affinity calculations. The binding affinities of these small molecules with P70-S6K1 & PI3K-δ were performed using AutoDock Vina. Among all the compounds, PP16 showed highest binding affinity of −14.7 kcal/mol with P70-S6K1 kinase & −17.2 kcal/mol with PI3K-δ kinases as compared to the molecules under clinical trials (PF-4708671 & IC-87114). Docking studies revealed that N-9 coumarine substituted purine derivative could be one of the potential ligands for the inhibition of P70-S6K1 & PI3K-δ kinases. Hence, this compound can be further investigated by in vitro and in vivo experiments for further validation.

Substituted quinolines containing a 1,2,4-triazole moiety were synthesized using reported methods. The molecular docking studies support the experimental results that these compounds are active against A. fumigatus and C. albicans where N-myristoyl transferase (NMT) and dihydrofolate reductase (DHFR), respectively, are the target enzymes. The analogues that contain methoxy and chloro substituents exhibit the best antifungal activity.

A series of new urea derivatives, containing aryl moieties as potential antimicrobial agents, were designed, synthesized, and characterized by 1H NMR, 13C NMR, FT-IR, and LCMS spectral techniques. All newly synthesized compounds were screened in vitro against five bacterial strains (Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Staphylococcus aureus) and two fungal strains (Candida albicans and Cryptococcus neoformans). Variable levels of interaction were observed for these urea derivatives. However, and of major importance, many of these molecules exhibited promising growth inhibition against Acinetobacter baumannii. In particular, to our delight, the adamantyl urea adduct 3l demonstrated outstanding growth inhibition (94.5%) towards Acinetobacter baumannii. In light of this discovery, molecular docking studies were performed in order to elucidate the binding interaction mechanisms of the most active compounds, as reported herein.

In present work, Surflex docking has been carried out on a series (23 compounds bearing N’-arylsubstituted pyrrole heterocyclic molecules) of M. tuberculosis inhibitors. SYBYL-X 2.0 package (Tripos Inc., St. Louis, USA) was used for the study. Surflex-docking shown that the peptide connection between the aryl substitution and pyrroly moiety was significant to exhibit receptor and molecular interactions, and it was also found that the pattern of binding of established compounds is same as that of the ligand 1-cyclohexyl-N-(3,5-dichlorophenyl)-5-oxopyrrolidine-3-carboxamide, which gives an idea in understanding the specific activity of compounds towards the receptor.

A series of new urea derivatives (3a-p) have been synthesized from readily available isocyanates and amines in good to high yields. All synthesized compounds were fully characterized using 1H NMR, 13C NMR, IR, and mass spectrometry. Additionally, the structure of the compound (3n) was confirmed by single-crystal X-ray diffraction. Furthermore, all compounds were evaluated for antimicrobial activity against five bacteria and two fungi. Last but not the least, molecular docking studies with Candida albicans dihydropteroate synthetase were performed and the results are presented herein.

Biomolecular interactions of carisoprodol (CAP) with bovine serum albumin (BSA) have been studied by fluorescence and UV-visible spectroscopy and confirmed by multispectroscopic methods including molecular docking studies. The intrinsic intensity of BSA was quenched by a dynamic quenching mechanism. The binding constant and number of binding sites were calculated according to the Stern–Volmer equation. The effect of β-cyclodextrin on the binding has been studied. Thermodynamic parameters were calculated which reveal the involvement of hydrophobic interactions in the binding. Based on Forster's theory of non-radiation energy transfer, the average binding distance (r) between BSA and CAP was evaluated. Spectral results showed that the binding of CAP to BSA induced conformational changes in BSA. A molecular docking study confirmed the drug binding sites and interaction of CAP with amino acid residues.

Novel series of pyrrole derivatives were synthesized with an approach to reduce the growing anti-tubercular resistance and to develop more potent and less side effect anti-tubercular agents. Herein, we synthesized a series of substituted 2-phenoxybenzamide derivatives (3a-j) by reacting different phenoxy acetic acids with 4-(-1H-pyrrol-1-yl)benzoate (2) and a series of pyrrolyl benzamides (6a-c) were synthesized by reacting 4-(1H-pyrrol-1-yl)benzoic acid with different hydrazides 2, (5a-b) using HBTU as a coupling agent, DIEA as a catalyst and DMF as a solvent. Structures of all the newly synthesized compounds were confirmed by spectral analysis viz., IR, 1H NMR, 13C NMR and Mass. Further they were tested for their anti-tubercular and antibacterial activities and compounds showed moderate to good activity.

A novel series of 6-chloro-7-methyl-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one derivatives were synthesized. Structure of the newly synthesized compounds was established by their analytical and spectroscopic data. The title compounds were evaluated for their anticancer activity against human breast cancer (T-47D) and lung cancer (NCI-H226) cell lines. Effects of compounds on the cell morphology of these cell lines were studied. Among the series of compounds tested, 6-chloro-7-methyl-2-(4-((2-(piperidin-1-yl)ethylamino)methyl) phenyl)-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one [MTDP4(9)] exhibited good anticancer activity against both cell lines. Further, the binding interaction of [MTDP4(9)] with bovine serum albumin has been investigated by UV, fluorescence and molecular docking studies.

Spectrum of each derivatives

Article history: With an objective of developing some novel analgesic and antiinflammatory natural agents with fast acting and low toxicity profile here in, the different extracts of Phaseolus vulgaris (Linn) seeds were evaluated for analgesic and antiinflammatory activities using glacial acetic acid induced writhing and carrageenan induced rat paw oedema method respectively. For screening of the extracts for analgesic and antiinflammatory activities aspirin and diclofenac were used as standard drugs respectively. Petroleum ether extract exhibited significant analgesic and antiinflammatory activities. The petroleum ether extract can be considered as a potential candidate for analgesic and antiinflammatory activities. The presence of steroids and flavonoids in petroleum ether extract of Phaseolus vulgaris Linn., seeds could be attributed for the analgesic and antiinflammatory activities.

The objective of this research work is to carryout the phytochemical screening and evaluate the analgesic, anti-inflammatory activities of Peganum harmala Linn., seeds. In this study different extracts of Peganum harmala (Linn) seeds were evaluated for analgesic and anti-inflammatory activities using glacial acetic acid induced writhing and carrageenan induced rat paw edema models respectively. For analgesic and anti-inflammatory activities aspirin and diclofenac were used as standard drugs respectively. The ethyl acetate extract showed significant analgesic and anti-inflammatory activities, thus it can be considered as a potential candidate for analgesic and antiinflammatory activities. The presence of alkaloids, steroids, flavonoids in ethyl acetate extract of Peganum harmala (Linn) seeds could be attributed for the claimed analgesic and anti-inflammatory activities.

In efforts to develop new antitubercular agents, we report here the synthesis of a series of novel pyrrole hydrazine derivatives. The molecules were evaluated against inhibitors of InhA, which is one of the key enzymes involved in type II fatty acid biosynthetic pathway of the mycobacterial cell wall as well as inhibitors of Mycobacterium tuberculosis H37Rv. The binding mode of compounds at the active site of enoyl-ACP reductase was explored using the surflex-docking method. The model suggests one or two H-bonding interactions between the compounds and the InhA enzyme. Some compounds exhibited good activities against InhA in addition to promising activities against M. tuberculosis.

Introduction:In efforts to develop new antitubercular (anti-TB) compounds, herein we describe cytotoxic evaluation of 15 newly synthesized pyrrolyl pyrazoline carbaldehydes.Method & Materials:Surflex-Docking method was used to study binding modes of the compounds at the active site of the enzyme enoyl ACP reductase fromMycobacterium tuberculosis (M. tuberculosis), which plays an important role in FAS-II biosynthetic pathway ofM. tuberculosisand also it is an important target for designing novel anti-TB agents.Results:Among the synthesized compounds, compounds4gand4ishowed H-bonding interactions with MET98, TYR158 and co-factor NAD+, all of which fitted well within the binding pocket of InhA. Also, these compounds have shown the same type of interaction as that of 4TZK ligand. The compounds were further evaluated for preliminary anti-TB activities againstM. tuberculosisH37Rv strain.Conclusion:Some compounds were also screened for their mammalian cell toxicity using human lung cancer cell-line (A549) that was found to be nontoxic.

Herein, we describe the successful design and synthesis of seventeen new 1,4-diazinanes, compounds commonly known as piperazines. This group of piperazine derivatives (3a-q) were fully characterized by 1H NMR, 13C NMR, FT-IR, and LCMS spectral techniques. The molecular structure of piperazine derivative (3h) was further established by single crystal X-ray diffraction analysis. All reported compounds were evaluated for their antibacterial and antifungal potential against five bacterial (Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa) and two fungal strains (Candida albicans and Cryptococcus neoformans). The complete bacterial screening results are provided. As documented, piperazine derivative 3e performed the best against these bacteria. Additionally, data obtained during molecular docking studies are very encouraging with respect to potential utilization of these compounds to help overcome microbe resistance to pharmaceutical drugs, as explicitly noted in this manuscript.

In this study, a series of novel scaffold-based 3-(((substituted phenyl)amino)methyl)-2-methylquinazolin-4(3H)-one compounds, 3a-3r, was synthesized, characterized, and screened for its in vitro activity against the H37Ra strain of Mycobacterium tuberculosis. A number of analogs were found to have highly potent anti-tuberculosis activity. Compound 3m in particular had potent activity equal to that of the standard anti-tuberculosis drug rifampicin. New leads can be generated with the model developed in this study and this model will be optimized with the eventual goal of preparing new anti-tuberculosis agents.

Shrinivas D Joshi, Sheshagiri R Dixit, Shivprasad Gadag, Venkatrao H Kulkarni, Tejraj M Aminabhavi Novel Drug Design and Discovery Laboratory, Department of Pharmaceutical Chemistry, SET’s College of Pharmacy, Dharwad, Karnataka, India Abstract: A novel series of pyrrole derivatives were designed and synthesized with an aim to overcome the growing antitubercular resistance and develop more potent antimicrobial agents. In this pursuit, a novel series of 4-(1H-pyrrol-1-yl)benzoic acid hydrazide Schiff bases were synthesized and reacted with copper acetate to form the respective copper complexes. The reaction of ethyl 4-(2,5-dimethyl-1H-pyrrol-1-yl)benzoate/ethyl-4-(1H-pyrrol-1-yl)benzoate with hydrazine hydrate produced ethyl 4-(2,5-dimethyl-1H-pyrrol-1-yl)benzohydrazide/ethyl 4-(1H-pyrrol-1-yl)benzohydrazide. The reaction of these hydrazides with different aldehydes yielded N’-(arylidene)-4-(2,5-dimethyl-1H-pyrrol-1-yl)benzohydrazides/N’-(arylidene)-4-(1H-pyrrol-1-yl)benzohydrazides. Furthermore, these Schiff bases were reacted with copper acetate to produce respective copper complexes. All the synthesized compounds were screened for antitubercular activity using microplate alamar blue assay method that showed reasonably good minimum inhibitory concentration (MIC) values ranging from 3.12 to 50 µg/mL compared to the standard drugs like pyrazinamide (MIC =3.125 µg/mL) and streptomycin (MIC =6.25 µg/mL). The selected compounds were evaluated for antibacterial activity against Staphylococcus aureus, Bacillus subtilis, Klebsiella pneumoniae, and Escherichia coli using the broth microdilution assay method. It was found that these compounds exhibited good antibacterial activities in the MIC range of 3.125 to >100 µg/mL when compared against standard drugs like ciprofloxacin and norfloxacin. Keywords: synthesis, Surflex-Dock, copper complexes, antimicrobial activities

Recently, heterogeneous catalysts have been explored eximiously in the synthesis of heterocyclic compounds. Therefore, here we used solid-supported heterogeneous silica sulfuric acid as a catalyst for the synthesis of Schiff's base of 3-chloroformylcoumarin in view of simplified procedure, reusability and acceptable efficiency, which are required in organic synthesis. An efficient and facile methodology is preferred for synthesis of a class of chromeno-3-substituted derivatives ( 1a–1l ) with good yields. The molecular docking results showed excellent binding interactions with the Mycobacterium tuberculosis InhA-D148G mutant (PDB: 4DQU). The same biomolecules were screened for their in vitro anti-tubercular activity against the M.tb H37Rv strain and antimicrobial studies. Physico-chemistry, toxicity prediction with IC50 value and bioactivity score were also calculated for title compounds. Most active compounds were further tested for cytotoxicity studies and exhibited low-level cytotoxicity against Vero cells. The suggested conjugates are promising lead compounds for the subsequent investigation in search of new anti-tubercular agents. All the conjugates were obtained within the range and followed the Lipinski rule of 5, indicating more ‘drug-like’ nature.

Enoyl acyl carrier protein reductase (ENR)is an essential type II fatty acid synthase (FAS-II) pathway enzyme that is an attractive target for designing novel antitubercular agents.Herein, we report sixty-eight novel pyrrolyl substituted aryloxy-1,3,4-thiadiazoles synthesized by three-step optimization processes. Three-dimensional quantitative structure-activity relationships (3D-QSAR) were established for pyrrolyl substituted aryloxy-1,3,4-thiadiazole series of InhA inhibitors using the comparative molecular field analysis (CoMFA).Docking analysis of the crystal structure of ENR performed by using Surflex-Dock in Sybyl-X 2.0 software indicates the occupation of pyrrolyl substituted aryloxy 1,3,4-thiadiazole into hydrophobic pocket of InhA enzyme. Based on docking and database alignment rules, two computational models were established to compare their statistical results. The analysis of 3D contour plots allowed us to investigate the effect of different substituent groups at different positions of the common scaffold. In vitro testing of ligands using biological assays substantiated the efficacy of ligands that were screened through in silico methods.

Shrinivas D Joshi, Sheshagiri R Dixit, Uttam A More, Devendra Kumar, Tejraj M Aminabhavi, Venkatrao H Kulkarni Novel Drug Design and Discovery Laboratory, Department of Pharmaceutical Chemistry, SET's College of Pharmacy, Sangolli Rayanna Nagar, Karnataka, India Abstract: Nicotinamide adenine dinucleotide reduced-dependent reduction of trans-2-enoyl acyl carrier protein (ACP) to yield nicotinamide adenine dinucleotide (NAD+) and reduced enoyl thioester-ACP substrate is catalyzed by the enoyl-ACP reductase (ENR) enzyme which is an important enzyme for type II fatty acid synthesis (FAS-II) (PubMed identifier 15139852). It is also a useful object for the discovery of antimicrobial drugs because of its fundamental role in the metabolism. Hence, inhibition of ENR might be a novel approach in developing antitubercular (anti-TB) drugs. Quinolines are the important class of heterocycles found in natural and synthetic products of various kinds. In this paper, docking and three-dimensional quantitative structure–activity relationship (3D-QSAR) (comparative molecular field analysis [CoMFA], comparative molecular similarity indices analysis [CoMSIA], and Topomer CoMFA) studies were performed on a set of quinoline hydrazones. According to docking studies, active site of the enzyme, amino acid residue TYR158, and co-factor NAD+ are important in binding with the ligand. Of all the compounds tested, compounds 45 and 46 have shown a docking score of 6.22, while compound 26 has a docking score of 6.09. The CoMFA model with steric and electrostatic field exhibited q2=0.617, r2=0.81; CoMSIA model displayed q2=0.631, r2=0.755; Topomer CoMFA model exhibited q2=0.644, r2=0.865 with a standard error of estimate (SEE) of 0.37. The docking results provided detailed structurally important binding features between quinoline hydrazones and the ENR enzyme. Our findings also provide useful hints and information for designing compounds with improved inhibitory activity.Keywords: quinoline hydrazones, enoyl-ACP reductase, docking, QSAR: CoMFA, CoMSIA, Topomer CoMFA

Shrinivas D Joshi,1 Uttam A More,1,2 Shailesh Sorathiya,1 Deepshikha Koli,1 Tejraj M Aminabhavi1 1Novel Drug Design and Discovery Laboratory, Department of Pharmaceutical Chemistry, Soniya Education Trust’s College of Pharmacy, Dharwad, India; 2Centre for Research and Development, Prist University, Thanjavur, Tamil Nadu, India Abstract: A novel series of pyrrolyl thiadiazoles was synthesized and tested for antimycobacterial activity against the Mycobacterium tuberculosis H37Rv strain, using the microplate Alamar blue assay method. Molecular docking and in vitro minimum inhibitory concentration assays revealed that these molecules can be primarily screened for ENR inhibition, using the score values and H-bond interactions with amino acid residues Tyr158, Met98, and cofactor NAD+, which are the key interactions. For most of the molecules, hydrophobic interaction is the key factor affecting their antitubercular activity. The activity of -OCH3, -NO2, -F, pyridine, and sulfonamide substituted derivatives was better than that of -CH3, -NH2, -Cl, and -Br substituted derivatives, as per experimental and docking studies. Molecular modeling studies are in agreement with their biological evaluations. Keywords: pyrroles, antitubercular activity, Surflex-Docking, enoyl-ACP reductase

A series of 4-(2,5-dimethylpyrrol-1-yl)/4-pyrrol-1-yl benzoic acid hydrazide analogs, some derived triazoles, azetidinones, thiazolidinones, and pyrroles have been synthesized in good yields and structures of these compounds were established by IR, 1 H NMR, 13 C NMR, mass spectral, and elemental analysis. These compounds were evaluated for their preliminary in vitro antibacterial, antifungal, and antitubercular activity against Mycobacterium tuberculosis H 37 Rv strain by the broth dilution assay method. Twenty one of these compounds displayed good antimicrobial activity, with a MIC value of 1-4 μg/ml. Several compounds 4c, 8-10, 15b-15h, and 16b-16d exhibited good in vitro antitubercular activity with MIC value 1-2 μg/ml. Further, some title compounds were also assessed for their cytotoxic activity (IC 50 ) against mammalian Vero cell lines and A 549 (lung adenocarcinoma) cell lines using the MTT assay method. The results revealed that these compounds exhibit antitubercular activity at non-cytotoxic concentrations.

In the present investigation, a series of 4-(4-pyrrol-1-yl/2,5-dimethyl-4-pyrrol-1-yl) benzoic acid hydrazide analogs, some derived oxadiazoles and azines have been synthesized in good yields and structures of these compounds were established by IR, 1H NMR, 13C NMR, mass spectral and elemental analysis. The newly synthesized title compounds were evaluated for their antimicrobial as well as antimycobacterial activities. Among the tested compounds, 6j and 9c displayed promising anti-tubercular activity. Further, some compounds were also assessed for their cytotoxic activity (IC50) against mammalian Vero cell lines and A549 (lung adenocarcinoma) cell lines using the MTT assay method. The results revealed that these compounds exhibit anti-tubercular activity at non-cytotoxic concentrations. The docking of inhibitors into InhA using Sybyl-X 2.0 software revealed the vital interactions and binding conformation of the inhibitors.